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MicroRNAs Expression Profile in MN1-Altered Astroblastoma

ORCID
0000-0002-6223-9952
Affiliation
Department of Radiological, Oncological and Anatomo-Pathological Sciences, University Sapienza of Rome, 00161 Rome, Italy;(S.M.);(M.A.)
Gianno, Francesca;
ORCID
0000-0002-4747-1032
Affiliation
Hematology/Oncology and Stem Cell Transplantation, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy
Miele, Evelina;
ORCID
0000-0001-7533-4660
Affiliation
Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy;(C.S.);
Sabato, Claudia;
ORCID
0000-0001-7265-6429
Affiliation
Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy;(C.S.);
Ferretti, Elisabetta;
ORCID
0000-0002-8872-6409
Affiliation
Department of Radiological, Oncological and Anatomo-Pathological Sciences, University Sapienza of Rome, 00161 Rome, Italy;(S.M.);(M.A.)
Minasi, Simone;
ORCID
0000-0001-5892-1281
Affiliation
Department of Radiological, Oncological and Anatomo-Pathological Sciences, University Sapienza of Rome, 00161 Rome, Italy;(S.M.);(M.A.)
Buttarelli, Francesca Romana;
Affiliation
Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy
Salerno, Debora;
Affiliation
Center for Life Nano- & Neuro-Science, Fondazione Istituto Italiano di Tecnologia (IIT), 16161 Rome, Italy
Pediconi, Natalia;
Affiliation
Research Unit of Clinical Immunology and Vaccinology, Academic Department of Pediatrics, Bambino Gesù Children’s Hospital, 00165 Rome, Italy
Pascucci, Giuseppe Rubens;
Affiliation
UMR INSERM U1052/CNRS 5286, Cancer Research Center of Lyon, 69008 Lyon, France
Guerrieri, Francesca;
Affiliation
Molecular Genetics and Functional Genomics, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy
Ciolfi, Andrea;
Affiliation
Institute of Biosciences and Bioresources, National Research Council, 06128 Perugia, Italy
Pizzi, Simone;
ORCID
0000-0002-5506-2001
Affiliation
Pediatric Unit, Fondazione IRCCS Istituto Nazionale Tumori, 20133 Milano, Italy(V.B.);
Massimino, Maura;
ORCID
0000-0003-1486-1736
Affiliation
Pediatric Unit, Fondazione IRCCS Istituto Nazionale Tumori, 20133 Milano, Italy(V.B.);
Biassoni, Veronica;
Affiliation
Pediatric Unit, Fondazione IRCCS Istituto Nazionale Tumori, 20133 Milano, Italy(V.B.);
Schiavello, Elisabetta;
Affiliation
Department of Woman and Child Health Sciences and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
Gessi, Marco;
ORCID
0000-0002-5035-2448
Affiliation
IRCCS Istituto di Scienze Neurologiche di Bologna, 40139 Bologna, Italy;
Asioli, Sofia;
ORCID
0000-0002-4408-2373
Affiliation
Hematology/Oncology, Cell Therapy, Gene Therapies and Hemopoietic Transplant, 586724 Bambino Gesù Children’s Hospital, 00165 Rome, Italy
Mastronuzzi, Angela;
ORCID
0000-0002-4810-1201
Affiliation
Department of Basic Medical Sciences, Neuroscience, and Sensory Organs, University of Bari School of Medicine, 70121 Bari, Italy
d’Amati, Antonio;
ORCID
0000-0001-8427-9691
Affiliation
Department of Life Science, Health, and Health Professions, Link Campus University, 00165 Rome, Italy;
Catanzaro, Giuseppina;
Affiliation
Pediatric Oncology Unit, Padova University, 35122 Padova, Italy
Viscardi, Elisabetta;
Affiliation
Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt, 10117 Berlin, Germany
Capper, David;
ORCID
0000-0001-5382-2380
Affiliation
Department of Radiological, Oncological and Anatomo-Pathological Sciences, University Sapienza of Rome, 00161 Rome, Italy;(S.M.);(M.A.)
Giangaspero, Felice;
Affiliation
Department of Radiological, Oncological and Anatomo-Pathological Sciences, University Sapienza of Rome, 00161 Rome, Italy;(S.M.);(M.A.)
Antonelli, Manila

Background/Objectives: Astroblastoma is a rare glial neoplasm more frequent in young female patients, with unclear clinical behaviors and outcomes. The diagnostic molecular alteration is a rearrangement of the Meningioma 1 ( MN1 ) gene. MicroRNAs (miRNAs) are important gene expression regulators with strong implications in biological processes. Here, we investigated microRNA expression, regulation, and biological processes correlated to target genes of deregulated miRNAs in MN1-altered astroblastoma. Methods: A cohort of 14 tumor samples, histologically classified as astroblastoma, was retrospectively collected and analyzed through their DNA methylation profiles. MiRNA expression profiles were then detected on MN1 -altered astroblastomas ( n = 8) and normal brain controls ( n = 2) by Nanostring technology and validated by RT-qPCR; then, the expression of deregulated miRNAs was correlated with clinical-pathological characteristics. Subsequently, the methylation status of promoters of deregulated miRNAs was investigated through a methylation profiling microarray. Finally, bioinformatics analysis was conducted to explore the biological processes (BPs) and target genes of differentially expressed miRNAs. Results: Eight MN -altered astroblastoma were identified. Thirty-nine miRNAs were deregulated in tumor samples compared to normal brain tissue. Downregulated microRNAs exhibited an association with an increased risk of recurrence. The promoter methylation status was investigated in 32/39 miRNAs: 14/32 were epigenetically deregulated. None of them were genetically regulated. Conclusions: MN1 -altered astroblastomas have an miRNA expression signature that identifies specific BPs and pathways. Our findings suggested that the involved pathways could be associated with clinical and pathological characteristics of MN1-altered astroblastomas. Also, the biology of this rare tumor could have potential implications on prognostic markers and therapy.

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